Introduction 

Plazomicin is a next-generation semisynthetic aminoglycoside antibiotic that is used to treat complicated urinary tract infections (cUTI) caused by multi-resistant bacteria. The chemical structure of plazomicin differ from those of classical aminoglycosides (amikacin, gentamicin, and tobramycin). Furthermore, plazomicin has an unsaturated hydroxyethyl group and a substitution with 4-amino-2-hydroxybutanoic acid which protects it from the attack of the aminoglycoside modifying enzymes. Hence, it is used to treat infections caused by Enterobacterales resistant to aminoglycosides. It also has activity against bacteria resistant to carbapenems and colistin. 

Aim

To describe the current state of the literature regarding the clinical and in vitro use of plazomicin to treat infections from pathogens resistant to conventional antibiotics

Patient Profile 

Method

Study Design

• The selection and analysed was divided in five phases:  
  1. first phase: formulation of the clinical question: “What is the current clinical use of plazomicin in severe infections with multidrug-resistant pathogens?”
  2. second phase: definition of the search strategy
  3. third phase: identification of the relevant studies
  4. fourth phase: relevant studies’ selection
  5. fifth phase: data synthesis and result presentation

Results 

• According to the data analysis, plazomicin was effectively used to treat complicated urinary tract infections, bloodstream infections, and ventilation-associated pneumonia
• The causative pathogens isolated from studies on clinical isolates tested with plazomicin included Enterobacterales (46.97% studies), Klebsiella pneumoniae (24.24% studies), Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii (4.55% each)
• Plazomicin showed activity against Carbapenem-resistant Enterobacteriaceae (CRE), multidrug-resistant bacteria, Carbapenemase-producing Klebsiella pneumoniae (KPC), extended-spectrum beta-lactamase Escherichia coli (ESBL-E) and methicillin-resistant Staphylococcus aureus (MRSA) in various trials
• Pathogens resistant to plazomicin were rarely encountered across these clinical trials; only six isolates cultured in the CARE trial (two from the plazomicin arm and four from the colistin arm) and seven isolates in the EPIC trial had baseline MICs resistant to plazomicin; resistance was linked to 16S rRNA methyltransferases
• It has demonstrated non-inferiority compared to meropenem for the treatment of cUTIs; Plazomicin can be a good option to treat cUTIs caused by pathogens with poor sensitivity to carbapenems
• Plazomicin is administered once daily, if not less frequently based on underlying renal function, and has a short 30-minute administration duration, resulting in a convenient treatment option for the outpatient antibiotic treatment (OPAT) setting

Safety 

• Three phase 1 studies on the safety profile and general pharmacology of plazomicin on healthy volunteers
• One study showed no change in the blood concentration of metformin with concomitant of plazomicin
• Two studies reported good tolerance of plazomicin even in patients with advanced kidney disease or on dialysis
• In EPIC trial, renal toxicity associated with plazomicin (renal impairment in 3% of patients) was similar to that caused by meropenem; however, renal damage caused by plazomicin was reversible and most patients (80%) already at the discharge visit after plazomicin treatment showed complete recovery of renal function
• No significant alterations seen in the QT length in a study evaluating the cardiac effect of plazomicin
• In the EPIC trial, the most common adverse events reported were decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%)
• Overall, serious adverse events (ototoxicity) reported in trials were documented in <2% of patients

Conclusion 

• Plazomicin is a new-generation semisynthetic aminoglycoside with activity against MDR Enterobacterales
• Plazomicin has emerged as a promising non-beta-lactam alternative for the treatment of infections caused by MDR Enterobacterales
• However, the review suggested that plazomicin should be administered only when necessary and used sparingly to have its effectiveness maintained over time

Life (Basel) 2022; 12(12): 1949